The goal of this project is to characterize the proteins that mediate macrophage fusion leading to the differentiation of giant cells & potentially osteoclast. The improved understanding of the fusion mechanism will facilitate the development of new therapeutic approaches to prevent diseases in which giant cells and osteoclasts are involved. The protein that potentially mediates sperm-oocyte fusion, PH30, has been cloned, and shown to share homology with the macrophage protein MS2. Because we have characterized a highly efficient macrophage fusion assay using rat macrophages, we propose to clone the rat macrophage cDNA homologue of pH- 30/mS2, characterize biochemically athe corresponding protein and establish cell lines transfected with this CDNA to study the role of this protein in fusion.